Comparative effects of the ω3 polyunsaturated fatty acid derivatives resolvins E1 and D1 and protectin DX in models of inflammation and pain

ω3 多不饱和脂肪酸衍生物消退素 E1 和 D1 以及保护素 DX 在炎症和疼痛模型中的比较作用

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作者:Flávia Cs Fonseca, Ricardo M Orlando, Regina Mm Turchetti-Maia, Janetti Nogueira de Francischi

Conclusion

Rvs, as analgesic agents, may be better therapeutic agents than nonsteroidal anti-inflammatory drugs, the current choice in the relief of pain of an inflammatory origin. However, the possibility of developing adverse effects cannot be overlooked.

Methods

The effects of Rvs E1 and D1 and protectin DX (PDX) were assessed in rat paws inflamed by the standard proinflammatory stimulus carrageenan or by histamine, 5-hydroxytryptamine, substance P or prostaglandin E2. The experimental outcomes were the mechanical nociceptive threshold and increase in paw volume as a measure of pain and edema formation, respectively. The analgesic and anti-inflammatory activities of the indicated SPMs were also compared with nonsteroidal (indomethacin and celecoxib) and steroidal (dexamethasone) anti-inflammatory drugs.

Purpose

Specialized pro-resolving lipid mediators (SPMs), also known as lipoxins, resolvins (Rvs), protectins and maresins, have been implicated in the resolution of the inflammatory process. However, a systematic comparison of their activity in the relief of inflammation and pain models is still lacking. Materials and

Results

Only RvE1 and RvD1 presented analgesic and anti-inflammatory activities in the carrageenan model, and RvE1 was twice as potent as RvD1. Both substances tended to be better analgesics than anti-inflammatory agents, with a modeling profile similar to steroidal anti-inflammatory drugs. However, proinflammatory effects (edema formation) were also detected when the mediators histamine, 5-hydroxytryptamine or substance P replaced carrageenan as the proinflammatory stimuli. The analgesic and anti-inflammatory effects of resolvins were specifically prevented by an antagonist of the leukotriene B4 receptor 1 (BLT1).

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